ALBERT

Description: NSC-87877 inhibits DUSP26 function in neuroblastoma resulting in p53-mediated apoptosis Cell Death and Disease 6, e1841 (August 2015). doi:10.1038/cddis.2015.207 Authors: Y Shi, I T Ma, R H Patel, X Shang, Z Chen, Y Zhao, J Cheng, Y Fan, Y Rojas, E Barbieri, Z Chen, Y Yu, J Jin, E S Kim, J M Shohet, S A Vasudevan & J Yang

Description: Ischemic postconditioning protects the heart against ischemia–reperfusion injury via neuronal nitric oxide synthase in the sarcoplasmic reticulum and mitochondria Cell Death and Disease 7, e2222 (May 2016). doi:10.1038/cddis.2016.108 Authors: L Hu, J Wang, H Zhu, X Wu, L Zhou, Y Song, S Zhu, M Hao, C Liu, Y Fan, Y Wang & Q Li

Description: Downregulation of FAP suppresses cell proliferation and metastasis through PTEN/PI3K/AKT and Ras-ERK signaling in oral squamous cell carcinoma Cell Death and Disease 5, e1155 (April 2014). doi:10.1038/cddis.2014.122 Authors: H Wang, Q Wu, Z Liu, X Luo, Y Fan, Y Liu, Y Zhang, S Hua, Q Fu, M Zhao, Y Chen, W Fang & X Lv

Description: Although immune checkpoint blockade has shown initial success for various cancers, only a small subset of patients benefits from this therapy. Some chemotherapeutic drugs have been reported to induce antitumor T cell responses, prompting a number of clinical trials on combination chemoimmunotherapy. However, how to achieve potent immune activation with traditional chemotherapeutics in a manner that is safe, effective, and compatible with immunotherapy remains unclear. We show that high-density lipoprotein–mimicking nanodiscs loaded with doxorubicin (DOX), a widely used chemotherapeutic agent, can potentiate immune checkpoint blockade in murine tumor models. Delivery of DOX via nanodiscs triggered immunogenic cell death of cancer cells and exerted antitumor efficacy without any overt off-target side effects. "Priming" tumors with DOX-carrying nanodiscs elicited robust antitumor CD8 + T cell responses while broadening their epitope recognition to tumor-associated antigens, neoantigens, and intact whole tumor cells. Combination chemoimmunotherapy with nanodiscs plus anti–programmed death 1 therapy induced complete regression of established CT26 and MC38 colon carcinoma tumors in 80 to 88% of animals and protected survivors against tumor recurrence. Our work provides a new, generalizable framework for using nanoparticle-based chemotherapy to initiate antitumor immunity and sensitize tumors to immune checkpoint blockade.

Description: Magnetic influences increase in importance in the solar atmosphere from the photosphere out into the corona, yet our ability to routinely measure magnetic fields in the outer solar atmosphere is lacking. We describe the scientific objectives and capabilities of the COronal Solar Magnetism Observatory (COSMO), a proposed synoptic facility designed to measure magnetic fields and plasma properties in the large-scale solar atmosphere. COSMO comprises a suite of three instruments chosen to enable the study of the solar atmosphere as a coupled system: 1) a coronagraph with a 1.5-m aperture to measure the magnetic field, temperature, density and dynamics of the corona; 2) an instrument for diagnostics of chromospheric and prominence magnetic fields and plasma properties; and 3) a white-light K-coronagraph to measure the density structure and dynamics of the corona and coronal mass ejections. COSMO will provide a unique combination of magnetic field, density, temperature and velocity observations in the corona and chromosphere that have the potential to transform our understanding of fundamental physical processes in the solar atmosphere and their role in the origins of solar variability and space weather.

Description: 〈span〉〈div〉Summary〈/div〉The 280-km-long San Cristobal Trough (SCT), created by the tearing of the Australia plate as it subducts under the Pacific plate near the Solomon and Vanuatu subduction zones, has hosted strike-slip earthquake sequences in 1993 and 2015. Both sequences, which likely represent a complete seismic cycle, began along the oldest section of the SCT—the portion farthest from the tear that has experienced the most cumulative displacement—and migrated to the younger sections closer to the tear. The SCT's abundant seismicity allows us to study transform boundary development—a process rarely observed along a single fault system—through observations of earthquake rupture properties. Using the spectral ratio method based on empirical Green's functions (EGFs), we calculate the corner frequencies of three M〈sub〉w〈/sub〉 ∼7 2015 earthquakes and co-located smaller earthquakes. We utilize two different spectral ratio stacking methods and fit both Brune and Boatwright models to the stacked spectral ratios. Regardless of stacking methods and spectral models, we find that the corner frequencies of the 2015 M〈sub〉w〈/sub〉 ∼7 earthquakes decrease slightly with distance from the tear. Assuming a constant rupture velocity and an omega-square spectral model, this corner frequency decrease may be due to an increase in rupture length with distance from the tear. The spectrum of the 2015 earthquake farthest from the tear also deviates from the omega-square model, which may indicate rupture complexity. Stress drop estimates from the corner frequencies of the 2015 M〈sub〉w〈/sub〉 ∼7 earthquakes range between 1 and 7 MPa, whereas stress drop estimates of their EGFs range from ∼0.05 to 10 MPa with most values between 0.1 to 1 MPa. Independent evidence from a second moments analysis of the 2015 earthquake sequence also indicates a possible increase in rupture length with distance from the tear, confirming the results from the spectral ratio analysis. We also observe an increase in normalized centroid time-delay values, a first-order proxy for rupture behavior, with distance from the tear for the 2015 sequence. A similar trend for the 1993 sequence suggests that earthquake rupture varies systematically along the SCT. Since distance from the tear corresponds to cumulative fault displacement, these along-strike rupture variations may be due to a displacement-driven fault maturation process.〈/span〉

Description: 〈span〉〈div〉Abstract〈/div〉Lower Triassic Feixianguan oolithic shoal complexes are widely developed in the northwestern Sichuan Basin, southwest China, where they host large natural gas reserves. To understand their development and the factors that controlled their deposition, we have used observations and interpretations of outcrops, cores, thin sections, well-log data, and seismic data to characterize the geologic and geophysical properties of the oolithic shoals of the Lower Triassic Feixianguan Formation in the Jiange area, northwestern Sichuan Basin. The oolithic shoals of the Feixianguan Formation are composed of locally dolomitized oolithic grainstones or packstones deposited in a semirestricted platform environment. With a thickness of more than 50 m, oolithic shoals mainly occur in the Fei 2 Member within the southeastern Jiange area. The results indicate that the shoals mainly lie above tectonic uplifts (caused by the northwest-trending basement-involved faults) and surrounding microtopographic highs. Furthermore, the prograding clinoforms and changes in accommodation space caused by sea-level fall influence the thickness of oolithic shoal deposits, and constrain their development in highstand systems tracts, resulting in their migration coinciding with the trend of clinoform progradation. We concluded that the development of oolithic shoals in the Jiange area may be controlled by two major factors: (1) the influence of paleotopography governed by the syndepositional faults on the accumulation of oolithic shoals and (2) the role of sea-level change in the migration of oolithic shoals.〈/span〉

Description: Author(s): H. B. Zhao, Y. Fan, G. Lüpke, A. T. Hanbicki, C. H. Li, and B. T. Jonker We report on observation of coherent longitudinal acoustic phonons in Fe/AlGaAs (001) heterostructure by time-resolved second-harmonic generation (TRSHG). The phonon induces not only a fast and highly damped oscillatory signal but also a long-lived one that exhibits an oscillating period identical t... [Phys. Rev. B 83, 212302] Published Tue Jun 28, 2011

Description: The transforming growth factor-β (TGF-β) signalling pathway participates in various biological processes. Dysregulation of Smad4, a central cellular transducer of TGF-β signalling, is implicated in a wide range of human diseases and developmental disorders. However, the mechanisms underlying Smad4 dysregulation are not fully understood. Using a functional screening approach based on luciferase reporter assays, we identified 39 microRNAs (miRNAs) as potential regulators of Smad4 from an expression library of 388 human miRNAs. The screening was supported by bioinformatic analysis, as 24 of 39 identified miRNAs were also predicted to target Smad4 . MiR-199a, one of the identified miRNAs, was inversely correlated with Smad4 expression in various human cancer cell lines and gastric cancer tissues, and repressed Smad4 expression and blocked canonical TGF-β transcriptional responses in cell lines. These effects were dependent on the presence of a conserved, but not perfect seed paired, miR-199a-binding site in the Smad4 3'-untranslated region (UTR). Overexpression of miR-199a significantly inhibited the ability of TGF-β to induce gastric cancer cell growth arrest and apoptosis in vitro , and promoted anchorage-independent growth in soft agar, suggesting that miR-199a plays an oncogenic role in human gastric tumourigenesis. In conclusion, our functional screening uncovers multiple miRNAs that regulate the cellular responsiveness to TGF-β signalling and reveals important roles of miR-199a in gastric cancer by directly targeting Smad4.

Description: Langmuir DOI: 10.1021/la302276n